Aerobic exercise is a promising intervention to attenuate frailty, but preclinical studies have used only male animals. We investigated the impact of voluntary aerobic exercise on frailty, biological age (FRailty Inferred Geriatric Health Timeline [FRIGHT] clock), predicted life expectancy (Analysis of FRAIlty and Death [AFRAID] clock), and mortality in both sexes and determined whether exercise was associated with changes in inflammation. Older (21–23 months) male (n = 12) and female (n = 22) C57Bl/6 mice matched for baseline frailty scores were randomized into exercise (running wheel) and sedentary (no wheel) groups. Frailty index scores were measured biweekly (13 weeks), and 23 serum cytokines were measured at midpoint and end point. Exercise levels varied between mice but not between the sexes. Exercise had no effect on mortality, but it attenuated the development of frailty in both sexes (female = 0.32 ± 0.04 vs 0.21 ± 0.01; p = .005; male = 0.30 ± 0.02 vs 0.22 ± 0.02; p = .042) and reduced frailty in older females after 10 weeks. FRIGHT scores were unaffected by exercise but increased with time in sedentary males indicating increased biological age. Exercise prevented the age-associated decline in AFRAID scores in older females such that exercised females had a longer life expectancy. We investigated whether aerobic exercise was associated with changes in systemic inflammation. Cytokine levels were not affected by exercise in males, but levels of pro-inflammatory cytokines were positively correlated with the frequency of exercise in females. Despite increases in systemic inflammation, exercise reduced frailty and increased life span in older females. Thus, voluntary aerobic exercise, even late in life, has beneficial effects on health in both sexes but may be especially helpful in older females.

中文翻译：

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有氧运动可减轻衰老雄性和雌性 C57Bl/6 小鼠的虚弱，并对系统细胞因子的影响因性别而异

有氧运动是一种有前途的减轻虚弱的干预措施，但临床前研究仅使用雄性动物。我们调查了自愿有氧运动对两性的虚弱、生物年龄（FRailty 推断老年健康时间线 [FRIGHT] 时钟）、预测预期寿命（FRAilty 和死亡分析 [AFRAID] 时钟）和死亡率的影响，并确定运动是否与炎症的变化有关。将与基线虚弱评分相匹配的较大（21-23 个月）雄性（n = 12）和雌性（n = 22）C57Bl/6 小鼠随机分为运动组（跑轮组）和久坐组（无轮组）。每两周（13周）测量衰弱指数评分，并在中点和终点测量23种血清细胞因子。小鼠之间的运动水平存在差异，但性别之间没有差异。运动对死亡率没有影响，但它减轻了两性衰弱的发展（女性 = 0.32 ± 0.04 vs 0.21 ± 0.01；p = .005；男性 = 0.30 ± 0.02 vs 0.22 ± 0.02；p = .042）并降低了死亡率10周后老年女性身体虚弱。久坐男性的 FRIGHT 分数不受运动影响，但随着时间的推移而增加，表明生物年龄增加。锻炼可以防止老年女性 AFRAID 分数与年龄相关的下降，从而使锻炼的女性的预期寿命更长。我们研究了有氧运动是否与全身炎症的变化有关。男性细胞因子水平不受运动影响，但女性促炎细胞因子水平与运动频率呈正相关。尽管全身炎症增加，但运动可以减轻老年女性的虚弱状况并延长寿命。因此，自愿的有氧运动，即使是在晚年，对两性的健康都有有益的影响，但对老年女性可能尤其有帮助。